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Extended schedule, escalated dose temozolomide versus dacarbazine in stage IV melanoma: Final results of a randomised phase III study (EORTC 18032)


Patel, P M; Suciu, S; Mortier, L; Kruit, W H; Robert, C; Schadendorf, D; Trefzer, U; Punt, C J A; Dummer, R; Davidson, N; Becker, Juergen; Conry, R; Thompson, J A; Hwu, W J; Engelen, K; Agarwala, S S; Keilholz, U; Eggermont, A M M; Spatz, A (2011). Extended schedule, escalated dose temozolomide versus dacarbazine in stage IV melanoma: Final results of a randomised phase III study (EORTC 18032). European Journal of Cancer, 47(10):1476-1483.

Abstract

PURPOSE: To compare the efficacy of an extended schedule escalated dose of temozolomide versus standard dose dacarbazine in a large population of patients with stage IV melanoma. PATIENTS AND METHODS: A total of 859 patients were randomised to receive oral temozolomide at 150mg/m(2)/day for seven consecutive days every 2weeks or dacarbazine, administered as an intravenous infusion at 1000mg/m(2)/day on day 1 every 3weeks. The primary endpoint was overall survival (OS), using an intent-to-treat principle. EudraCT number 2004-000654-23 NCI registration number NCT00005052. RESULTS: Median OS was 9.1months in the temozolomide arm and 9.4months in the dacarbazine arm, with a hazard ratio (HR) of 1.00 (95%confidence interval [CI]: 0.86, 1.17; P=0.99). Median progression-free survival (PFS) was 2.3months in the temozolomide arm and 2.2months in the dacarbazine arm, with a HR of 0.92 (95%CI: 0.80, 1.06; P=0.27). In patients with measurable disease, overall response rate was higher in the temozolomide arm than in the dacarbazine arm (14.5% versus 9.8%, respectively), but the median duration of response was longer for dacarbazine. The extended schedule, escalated dose temozolomide arm showed more toxicity than the standard dose, single agent dacarbazine arm. The most common non-haematological treatment emergent adverse events reported in both treatment arms were nausea, fatigue and vomiting and constipation. CONCLUSION: Extended schedule escalated dose Temozolomide (7days on 7days off) is feasible and has an acceptable safety profile, but does not improve OS and PFS in metastatic melanoma when compared to standard dose dacarbazine.

Abstract

PURPOSE: To compare the efficacy of an extended schedule escalated dose of temozolomide versus standard dose dacarbazine in a large population of patients with stage IV melanoma. PATIENTS AND METHODS: A total of 859 patients were randomised to receive oral temozolomide at 150mg/m(2)/day for seven consecutive days every 2weeks or dacarbazine, administered as an intravenous infusion at 1000mg/m(2)/day on day 1 every 3weeks. The primary endpoint was overall survival (OS), using an intent-to-treat principle. EudraCT number 2004-000654-23 NCI registration number NCT00005052. RESULTS: Median OS was 9.1months in the temozolomide arm and 9.4months in the dacarbazine arm, with a hazard ratio (HR) of 1.00 (95%confidence interval [CI]: 0.86, 1.17; P=0.99). Median progression-free survival (PFS) was 2.3months in the temozolomide arm and 2.2months in the dacarbazine arm, with a HR of 0.92 (95%CI: 0.80, 1.06; P=0.27). In patients with measurable disease, overall response rate was higher in the temozolomide arm than in the dacarbazine arm (14.5% versus 9.8%, respectively), but the median duration of response was longer for dacarbazine. The extended schedule, escalated dose temozolomide arm showed more toxicity than the standard dose, single agent dacarbazine arm. The most common non-haematological treatment emergent adverse events reported in both treatment arms were nausea, fatigue and vomiting and constipation. CONCLUSION: Extended schedule escalated dose Temozolomide (7days on 7days off) is feasible and has an acceptable safety profile, but does not improve OS and PFS in metastatic melanoma when compared to standard dose dacarbazine.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Dermatology Clinic
Dewey Decimal Classification:610 Medicine & health
Language:English
Date:2011
Deposited On:28 Jul 2011 12:08
Last Modified:07 Dec 2017 08:41
Publisher:Elsevier
ISSN:0959-8049
Publisher DOI:https://doi.org/10.1016/j.ejca.2011.04.030
PubMed ID:21600759

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